The process of programmed cell death or apoptosis has been shown to be centrally involved in the pathogenesis of the significant majority of human illnesses and injury states. The cellular attrition observed in most degenerative conditions is apoptotic in nature; conversely, a failure of apoptosis has been proposed to underlie many forms of cancer. The central role of apoptosis in human disease clearly brings with it clinical promise; for example, the strong possibility exists that attenuation of apoptotic death will significantly modulate the severity of degenerative disorders.
Abnormal regulation of apoptosis is a cause of several diseases, including cancer and neurodegenerative disorders among others. Bax is a 21-kDa member of the conserved Bcl-2 family of proteins involved in regulating programmed cell death. Bax plays a key role in the intrinsic pathway of apoptosis. Bcl-2 family proteins are characterized by the presence of four Bcl-2 homology (BH) domains. Antiapoptotic members (e.g., Bcl-2, Bcl-XL and Mcl-1) have all four BH domains (BH1-4). The proapoptotic members are further divided into multi-domain proteins (e.g., Bax, Bak and Bok) containing three BH domains (BH 1-3) or BH3-only proteins (e.g., Bim, Bid and PUMA, etc.,) containing just the BH-3 domain. The molecular mechanisms, by which these proteins function and interact is not fully understood, but their role in apoptosis is indisputable. Although it has been extensively studied how Bcl-2 family proteins influence each other, it is not well known how these proteins are regulated by non-Bcl-2 family proteins.